Carbepenems & Monobactams
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| Carbepenem drugs | Imipenem/Cilastatin (Primaxin)
Meropenem (Merrem)
Doripenem (Doribax)
Ertapenem (Invanz)
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| Monobactam drugs | Aztreonam (Azactam)
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| Carbepenem MoA | bactericidal B-lactams (stable b/c C-base)
Cell wall active (inhibit synthesis)
bind to PBPs; inhibit wall-building enzymes
Go thru porin protein channels; enter periplasmic space
synergistic w/ aminoglycosides (G+/-); additive w/ quinolones (G-)
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| Mech of Resistance to Carbepenems | Beta-lactamase
Altered cell wall penetration
PBP affinity alteration
Altered porin channels for gram negatives
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| Cilastin | dehydropeptidase inhibitor (not a beta lactamase inhibitor).
Added to imepenem to prevent its breakdown in kidney
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| Imipenem | zwitterion: better G- penetration
very broad spectrum!
synergistic combination
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| Primaxin (Imipenem/Cilastin) SoA | ESBLs! Staph, Strep, Pneumococci, B. Fragilis, Listeria, Pseudomonas
Enterococcus faecalis is ok, faecium coverage poor
SPACE (covers pseudomonas, G-)
Doesn't cover MRSA, VRE (faecium), C. dif, S. maltophilia, B. cepacia, atypicals, carbenemase-p
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| Primaxin (Imipenem/Cilastin) ADRs | leads to overgrowth of S. maltiphilia & B. cepacia (need to be Tx'd with Septra) seen in cystic fibrosis kids
Renal dysfxn (CrCl<20) -> accumulation -> seizure
IM infusion irritation: give w/ Lidocaine b/c it burns
N&V
Cross rxn w/ pen allergy
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| Imipenem PK | Cleared by kidney! Renal damage may lead to SEIZURES b/c of drug accumulation. Do NOT use in ptx with meningitis!!
Concentration INdepedent (time-dependent) b/c beta-lactam
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| Meropenem (Merrem) | zwitterion
resistant to dehydropeptidase so it doesn't need Cilastin for stability; thus, reduced seizure risk b/c quicker clearance
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| Meropenem (Merrem) SoA | Meningitis caused by:
Strep. pneumonia
Listeria (1st line is Septra. Meropenem is 2nd in case of septra allergy)
Can treat B. cepacia (from imipenem use)
More G- (pseudomonas), less Enterococcus activity than Imipenem (don't use)
ESBL
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| Doripenem (Doribax) SoA | close to Meropenem's SoA
Most active for B. cepacia
Mainly used for Pseudomonas
Can treat ESBL
Not used as often for meningitis as meropenem
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| Doripenem (Doribax) PK | Dose adjust for Renal impairment
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| Ertapenem (Invanz) SoA step down penem; more similar to 2nd/3rd Ceph b/c it doesn't cover entercoccus at all | Mainly for IAB or pelvic infections
also for diabetic foot infections
Can Tx UTI/pyelonephritic ESBL, but not systemic ESBL
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| Ertapenem (Invanz) | empiric use in community intra-abdominal infections like acute appendix
NOT for severe systemic or institutional Enterococcus & Pseudomonas infectoin
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| Ertapenem (Invanz) PK | Dose adjusted in renal patients
Given IM with lidocaine
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| Ertapenem (Invanz) ADRs | Headache
Diarrhea/Nausea fairly frequent
Phlebitis
Increased LFT’s low incidence but happens
CNS: tremors, dyskinesias, myoclonus
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| Aztreonam (Azactam) SoA | Pseudomonas
Enterobacter
E. coli
non ESBL producing organisms
NDM-1
Carbepenemase-producers
Must be combined w/ AGs for effective activity
Not for ESBL, or atypicals
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| Aztreonam (Azactam) PK | Concentration INdependent (beta-lactam)
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| Aztreonam MoA | Binds PBP like beta-lactamase
Must be combined w/ AGs for effective activity
(should NOT be combined with PCNs or Cephs b/c NO synergistic effect)
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| Aztreonam (Azactam) ADRs | Monitor PT/INR
Phlebitis
Pyrexia (fever), esp in kids
Good: No PCN allergy cross-over!
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